This project is concerned with the cellular control mechanisms by which stimuli cause the release of hormones and digestive enzymes and the similar mechanisms which mediate the action of many hormones. Specifically, work is focussed on Ca2 ion as the intracellular mediator of the action of cholecystokinin and acetylcholine to stimulate enzyme secretion by pancreatic acinar cells. Studies of initial receptor interactions are being carried out using radioiodinated cholecystokinin prepared by conjugation with iodinated Bolton-Hunter reagent. This ligand binds to high affinity receptors on isolated pancreatic acini and correlates with amylase release. Mobilization of cellular CA2 ion in response to receptor activation is being studied using 45Ca2 ion and atomic absorption spectrometry. The transport of calcium by isolated subcellular fractions is also being studied. These studies suggest that receptor activation leads to release of Ca2 ion from a microsomal component with a resulting rise in cytoplasmic Ca2 ion leading to secretion. The role of microtubules and microfilaments in this process is also being studied.